Risk Factors For Uterine Fibroids Research Articles

Risk factors for uterine fibroids

Risk factors for uterine fibroids

Population-based study of the reproductive risk factors for transvaginal ultrasound diagnosed uterine fibroids in Nigerian women

There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74–0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24–0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35–0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27–0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01–1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.

Modeling the Incidence of Uterine Fibroids among Women in the US

Heavy menstrual bleeding (HMB) and poor uterine receptivity and implantation, which results in infertility, are two of the most prevalent benign neoplasms of the uterus that impact millions of women in the United States and around the world. The primary aim of this study is to model the incidence of uterine fibroids among women in the US. The secondary data collected for this study on possible factors associated with Uterine fibroid was extracted from the US department of health from the period of December 2018 to December 2022. The multivariate logistic regression model was adopted which indicates that the incidence of Uterine Fibroids is significantly associated with health risk factors and socioeconomic factors like family history, age, and adult women. Meanwhile, Vitamin D Deficiency has an odd ratio of about 2.4 which is higher than the other risk factors considered in the study. Consequently, American adults’ women must monitor their lifestyle, have their BMI, Vitamin D deficiency, and other risk factors for uterine fibroids diagnosed, and then make sure they are receiving adequate treatment to prevent the tendency to develop uterine fibroids, which in turn will lower infertility due to the incidence uterine fibroids. Keywords: Uterine Fibroids, Logistic regression, odd ratio, Health and socioeconomic risk factors. DOI: 10.7176/JHMN/108-04 Publication date: May 31 st 2023

Epidemiology of uterine fibroid in black African women: a systematic scoping review

ObjectiveStudies, mainly from high-income countries, suggest that there are ethnic and racial variations in prevalence of uterine fibroids (UF). However, there have been few studies of the epidemiology of UF...

The effect of vitamin D on recurrence of uterine fibroids: A randomized, double-blind, placebo-controlled pilot study

Backgroundand purpose: A deficiency of vitamin D has been suggested as one of the principal risk factors for uterine fibroids (UFs). We aimed to investigate the effect of vitamin D supplementation on the recurrence of UFs. Materials and methodsIn a randomized, double-blind, placebo-controlled pilot study, women who had undergone hysteroscopic myomectomy from November 2017 to June 2020 were randomly given either vitamin D (1000 IU tablet; n = 55), or placebo (n = 54) daily for 12 months. Both groups were followed and compared in regard of the primary outcomes of the study, which were recurrence rates, size, and numbers of UFs based on three-dimensional transvaginal ultrasound investigation (3D-TVS). Data analysis was performed by the intention-to-treat (ITT) approach. ResultsThe mean age of the study participants was 37.9 ± 6.5 years. The two groups did not differ significantly in terms of demographic and pre-intervention clinical characteristics. The administration of vitamin D supplements for one year reduced recurrence rates of UFs by 50% (p = 0.17). Vitamin D also reduced the size of recurrent UFs in the intervention group compared to controls (−7.7 mm), the difference was statistically different (p < 0.001). No adverse effect of vitamin D was reported in the present study. ConclusionBased on these results, vitamin D appears to be a promising and safe agent in the prevention of recurrence and reduction of the size of recurrent UFs, although further well-designed and appropriately powered studies are required to demonstrate a significant difference in the size and number of recurrent UFs.

Investigation on factors related to uterine fibroids in rural women of northern Anhui province.

Given the increasing prevalence of hysteromyoma among the Chinese rural women of childbearing age, it is imperative that more attention should be given to researching risk factors that predispose women to this condition so that early preventive measures may be taken. Our study investigates potential risk factors for uterine fibroids such as participants' demographic characteristics (age, ethnicity, education), physiological characteristics (age at menarche, primiparous age), and the occurrence of several different female reproductive diseases (vaginitis, pelvic inflammatory disease). 2200 rural women of reproductive age were screened from a cross-sectional study carried out in the northern Anhui province. Data were collected by questionnaire surveys, gynecological and laboratory examinations and were subjected to univariate and multivariate analysis to evaluate the risk factors for uterine fibroids. Of the 2200 women, 440 had uterine fibroids. In general, women with endometriosis, ovarian cysts and early menarche were more likely to suffer from hysteromyoma. Factors including higher parity, late age of first childbirth, and a regular menstrual cycle were associated with the reduced risk of uterine fibroids. Our findings indicate that parameters such as earlier age of menarche, early primiparous age, lower parity and a variety of female reproductive diseases were associated with an increased risk of uterine fibroids. These findings may be used to guide the formulation of effective prevention and intervention protocols to improve the reproductive health of rural women.

Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids.

Uterine fibroids (UFs) are the most prevalent gynecologic neoplasm, affecting 70-80% of women over their lifespan. Although UFs are benign they can become life-threatening and require invasive surgeries such as myomectomy and hysterectomy. Notwithstanding the significant negative influence UFs have on female reproductive health, very little is known about early events that initiate tumor development. Several risk factors for UFs have been identified including vitamin D deficiency, inflammation, DNA repair deficiency, and environmental exposures to endocrine-disrupting chemicals (EDCs). EDCs have come under scrutiny recently due to their role in UF development. Epidemiologic studies have found an association between increased risk for early UF diagnosis and in utero EDC exposure. Environmental exposure to EDCs during uterine development increases UF incidence in a UF animal model. Notably, several studies demonstrated that abnormal myometrial stem cells (MMSCs) are the cell origin for UFs development. Our recent studies demonstrated that early-life EDC exposure reprogrammed the MMSCs toward a pro-fibroid landscape and altered the DNA repair and inflammation pathways. Notably, Vitamin D3 (VITD3) as a natural compound shrank the UF growth concomitantly with the reversion of several abnormal biological pathways and ameliorated the developmental exposure-induced DNA damage and pro-inflammation pathway in primed MMSCs. This review highlights and emphasizes the importance of multiple pathway interactions in the context of hypovitaminosis D at the MMSCs level and provides proof-of-concept information that can help develop a safe, long-term, durable, and non-surgical therapeutic option for UFs.

Treatment approved for heavy menstrual bleeding associated with fibroids

Oriahnn (AbbVie) is the first and only FDA-approved oral treatment for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. The treatment is a combination capsule containing elagolix 300 mg, estradiol 1 mg, and norethindrone 0.5 mg for the morning dose copackaged with a capsule of elagolix 300 mg for the evening dose. Uterine fibroids, common benign tumors in premenopausal women, can have a significant impact on quality of life, with symptoms such as heavy menstrual bleeding, pain, and bowel and bladder issues. Treatment options have included various surgical procedures such as hysterectomy and myomectomy, and medical therapies to reduce heavy menstrual bleeding (e.g., hormonal contraceptives, tranexamic acid, and NSAIDs). “Although surgical treatments, such as hysterectomy, are available, patients may not qualify for surgery or want the procedure,” said Christine P. Nguyen, MD, acting director, division of Urology, Obstetrics and Gynecology in FDA’s Center for Drug Evaluation and Research in an FDA news release. She noted that “various non-surgical therapies are used to treat fibroid-related heavy menstrual bleeding, but none have been FDA-approved specifically for this use.” The approval of Oriahnn now offers patients a nonsurgical option to help manage their condition. Uterine fibroids can be detected in up to 80% of women by the age of 50. Their growth is dependent on estrogen and progesterone, with the prevalence of fibroids increasing during a woman’s reproductive years. Race has also been identified as a risk factor for uterine fibroids, with Black women having a higher lifetime prevalence of fibroids and more severe symptoms compared with white women. Although some women may be asymptomatic, it is estimated that 20% to 50% of women seek either surgical or nonsurgical treatment to manage their symptoms. Oriahnn contains a gonadotropin-releasing hormone receptor antagonist (elagolix 300 mg), an estrogen (estradiol 1 mg), and a progestin (norethindrone acetate 0.5 mg). The elagolix results in a dose-dependent suppression of luteinizing hormone and follicle-stimulating hormone, leading to decreased concentrations of estradiol and progesterone and reduced bleeding associated with the uterine fibroids. The inclusion of estradiol and norethindrone in the morning dose helps achieve a balance between the reduction of heavy menstrual bleeding and associated hypoestrogenic adverse effects. The labeling states that the estradiol may reduce the bone loss that may occur with the reduction in estrogen levels from the elagolix, and the norethindrone may work to protect the uterus from the potential adverse endometrial effects from unopposed estrogen. The treatment may be given for up to 24 months. Approval was based on data from two randomized Phase III trials that evaluated data from 591 premenopausal women with heavy menstrual bleeding who were treated with elagolix 300 mg, estradiol 1 mg, and norethindrone 0.5 mg in the morning and elagolix 300 mg in the evening or placebo for 6 months. In both trials, more women who received the active treatment had reductions in menstrual blood loss compared with placebo from baseline to the final month of treatment. The most common adverse effects with Oriahnn from the clinical trials were hot flushes, headache, fatigue, and irregular vaginal bleeding. Numerous warnings and precautions are also listed in the label, with bone loss being one of them because of duration-dependent decreases in bone mineral density that may occur due to low estrogen levels. This effect may not be reversible and is the reason for limiting treatment to 24 months. Other warnings and precautions include thromboembolic disorders and vascular events, mood disorders, elevated blood pressure, and changes in menstrual bleeding patterns and the reduced ability to recognize pregnancy. Women should be counseled to use nonhormonal contraception while receiving treatment and for one week after discontinuing the drug.

Prevalence of Risk Factors for Uterine Fibroids at Tertiary Care Teaching Hospital: A Cross-sectional Study

: Objectives: To examine the prevalence of risk factors in patients suffering from uterine fibroid at tertiary care teaching hospital. Methods: A crosssectional study carried out between June to December 2019 includes patients who were diagnosed with uterine fibroids in the gynecology department, SVIMS, Tirupati. The position and number of the fibroids were counted and noted by the reports of Ultrasound examinations. Especially we assessed the prevalence of risk factors for uterine fibroids based on the questionnaire filled by the patients. The data were processed with the statistical program SPSS 25 and P value less than 0.05 were considered to be statically significant. Results: A total of 137 patients was studied, the majority of subjects were below the age group of 36-50 years (63.5%) followed by 21-35 years (24.08%) and 51-65 years (12.4%). The average age of the participants was 42.08 ± 8.89 years. BMI showed that women with 25 kg/m2 to 29.9 kg/m2 (54.74%) and ≥30 kg/m2 (8.75%) experienced a higher prevalence of fibroids (χ2 =11.55, P =0.003) than women with 18.5 kg/m2 to 24.9 kg/m2 (36.49%). The average body mass index (BMI) of women with fibroids that were detected in our study was 27.5kg/m2. Other risk factors were not significantly linked with uterine fibroids. Conclusion: Fibroid prevalence had a significant correlation with age and BMI. Early detection and reduced body weight may bring down the occurrence of uterine fibroids.Key words: Uterine fibroids, Cross-sectional study, Risk factors, Obesity, Body Mass Index (BMI).

A nongenomic mechanism for "metalloestrogenic" effects of cadmium in human uterine leiomyoma cells through G protein-coupled estrogen receptor.

Cadmium (Cd) is a ubiquitous environmental metal that is reported to be a "metalloestrogen." Uterine leiomyomas (fibroids) are estrogen-responsive gynecologic neoplasms that can be the target of xenoestrogens. Previous epidemiology studies have suggested Cd may be associated with fibroids. We have shown that Cd can stimulate proliferation of human uterine leiomyoma (ht-UtLM) cells, but not through classical estrogen receptor (ER) binding. Whether nongenomic ER pathways are involved in Cd-induced proliferation is unknown. In the present study, by evaluating G protein-coupled estrogen receptor (GPER), ERα36, and phospho-epidermal growth factor receptor (EGFR) expression in human tissues, we found that GPER, ERα36 and phospho-EGFR wereallhighly expressed in fibroids compared to patient-matched myometrial tissues. In ht-UtLM cells, cell proliferation was increased by low doses of Cd (0.1µM and 10µM), and this effect could be inhibited by GPER-specific antagonist (G15) pretreatment, or silencing (si) GPER, but not by siERα36. Cd-activated MAPK was dependent on GPER/EGFR transactivation, through significantly increased phospho-Src, matrix metalloproteinase-2 (MMP2) and MMP9, and heparin-binding EGF-like growth factor (HB-EGF) expression/activation. Also, phospho-Src could interact directly to phosphorylate EGFR. Overall, Cd-induced proliferation of human fibroid cells was through a nongenomic GPER/p-src/EGFR/MAPK signaling pathway that did not directly involve ERα36. This suggests that Cd may be a risk factor for uterine fibroids through cross talk between hormone and growth factor receptorpathways.

Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment.

Uterine fibroids (UFs) are the most common benign neoplastic threat to women's health and associated with DNA damage and genomic instability. Hypovitaminosis D is a known risk factor for UFs, especially among African Americans. Vitamin D3 has been shown to effectively inhibit UF phenotype, but its mechanisms remain unclear. We hypothesize that Vitamin D3 ameliorates UFs by recovering the damaged DNA repair system, thus inhibits tumor progression. We compared the DNA damage status and Vitamin D receptor (VDR) expression between normal myometrial and UF primary cells. Unrepaired DNA double-strand breaks (DSBs) accumulated but VDR expression decreased in UFs. The RNA and protein levels of key DNA repair members belonging to DNA DSB sensors (MRE11, NBS1, RAD50), mediators and effectors (CHECK2, BRCA1, RAD51) were downregulated in UFs compared with myometrial cells. VDR KD induced DSB accumulation and DNA damage response (DDR) defects in myometrial cells. Using the DNA damage PCR array, the expression of many additional DNA repair genes was downregulated in VDR KD cells. Treatment of UF cells with Vitamin D3 (100 nM) significantly decreased DNA damage and restored DDR concomitant with VDR induction. Notably, the PCR array demonstrated that among 75 downregulated genes after VDR KD, 67 (89.3%) were upregulated after vitamin D3 treatment. These studies demonstrate a novel link between DNA damage and the vitamin D3/VDR axis in UFs. Vitamin D3 suppresses the UF phenotype through orchestrated targeting at multiple molecules in DNA repair pathways, thus offering novel mechanistic insights into the clinical effectiveness of vitamin D3 on UFs.

ПРОГНОЗУВАННЯ РЕЦИДИВУ МІОМИ МАТКИ ПІД ЧАС ВАГІТНОСТІ

Міома матки зустрічається у 15–45 % жінок репродуктивного віку, посідаючи, таким чином, друге місце у структурі гінекологічної патології. За даними О. Л. Карякіної, основними чинниками ризику виникнення міоми матки є вік жінки більше 30 років, супутні гінекологічні захворювання, гіперменструальний синдром, більше 2 абортів в анамнезі.Мета дослідження – розробити модель росту міоматозних вузлів під час вагітності.Матеріали і методи. Дослідження проведено на базі Обласного перинатального центру (м. Одеса). Проаналізовано 267 історій пологів жінок, які народжували у термін з 2007 до 2016 р., та мали верифіковану міому матки на прегравідарному етапі, видалену шляхом консервативної міомектомії. Оцінювали результати УЗД, виконаного під час вагітності, за наявності відповідних документальних свідчень – більш ранні УЗД. Враховували кількість міоматозних вузлів, їх розміри на прегравідарному етапі та під час вагітності. Об’єм міоми визначали на підставі ультрасонографічних вимірювань за формулою для еліпсоїда: V=0,52 х a х b х c, де а – висота, b – ширина, c – товщина вузла, 0,52=π/2х3. Статистичну обробку проводили за допомогою регресійного та багатофакторного аналізу з використанням програмного забезпечення Statistica 10.0 (DellStatSoftInc., США).Результати досліджень та їх обговорення. За даними ретроспективного аналізу, середній вік жінок, оперованих на прегравідарному етапі з приводу міоми матки, склав (33,7±2,2) року. Рецидив міоми виник у 89 (33,3 %). Кількість міоматозних вузлів, виявлених під час вагітності, в середньому складала 1,8±0,2. При цьому середні розміри їх були (6,3±0,2) мм х (4,2±0,1) мм х (4,4±0,1) мм, що відповідає середньому об’єму (0,49±0,02) см3. У 49 (55,1 %) вагітних із рецидивом міоми протягом ІІ триместру відбулося збільшення міоматозних вузлів у середньому на (28,6±1,3) %. Цікаво, що найбільші розміри цих вузлів спостерігалися у терміні гестації 20 тижнів, натомість перед пологами розміри пухлини зменшувалися в середньому на (14,8±0,4) %. При розробці моделі розрахунку ризику рецидиву ми враховували дані гормонального профілю жінок, тривалості захворювання, наявності попередніх вагітностей, УЗД, у тому числі доплерометричних характеристик, результати “потрійного” тесту. Після проведених розрахунків одержали таке рівняння: 𝑋𝑋= 𝑒𝑒𝑞𝑞 1+𝑒𝑒𝑞𝑞 , де q = 6,6–0,3 A–0,5 LV–1,5 S–0,9 E + 0,6 PL, де A – вік жінки; LV – лінійна швидкість кровотоку в маткових артеріях; S – сумарний розмір міоматозних вузлів E – співвідношення рівня естріолу та його максимального референтного рівня; PL – співвідношення рівня плацентарного лактогену та його максимального референтного рівня. При значеннях X&gt;1,0 ризик рецидивування міоми під час вагітності є високим. Подальша перевірка коректності моделі показала, що її точність складає 0,94 (χ2=2,8 df=11 Pr&gt;χ2). Це дозволяє рекомендувати її для потреб клінічного прогнозування.Висновки. Найбільш значущими факторами рецидивування міоми під час вагітності є вік жінки, лінійна швидкість кровотоку в маткових артеріях, розмір міоматозних вузлів, рівень секреції естріолу та плацентарного лактогену. Розроблений алгоритм прогнозування дозволяє визначати ризик рецидиву міоми під час вагітності з точністю 0,94.

African genetic ancestry interacts with body mass index to modify risk for uterine fibroids.

Race, specifically African ancestry, and obesity are important risk factors for uterine fibroids, and likely interact to provide the right conditions for fibroid growth. However, existing studies largely focus on the main-effects rather than their interaction. Here, we firstly provide evidence for interaction between categories of body mass index (BMI) and reported-race in relation to uterine fibroids. We then investigate whether the association between inferred local European ancestry and fibroid risk is modified by BMI in African American (AA) women in the Vanderbilt University Medical Center bio-repository (BioVU) (539 cases and 794 controls) and the Coronary Artery Risk Development in Young Adults study (CARDIA, 264 cases and 173 controls). We used multiple logistic regression to evaluate interactions between local European ancestry and BMI in relation to fibroid risk, then performed fixed effects meta-analysis. Statistical significance threshold for local-ancestry and BMI interactions was empirically estimated with 10,000 permutations (p-value = 1.18x10-4). Admixture mapping detected an association between European ancestry and fibroid risk which was modified by BMI (continuous-interaction p-value = 3.75x10-5) around ADTRP (chromosome 6p24); the strongest association was found in the obese category (ancestry odds ratio (AOR) = 0.51, p-value = 2.23x10-5). Evaluation of interaction between genotyped/imputed variants and BMI in this targeted region suggested race-specific interaction, present in AAs only; strongest evidence was found for insertion/deletion variant (6:11946435), again in the obese category (OR = 1.66, p-value = 1.72x10-6). We found nominal evidence for interaction between local ancestry and BMI at a previously reported region in chromosome 2q31-32, which includes COL5A2, and TFPI, an immediate downstream target of ADTRP. Interactions between BMI and SNPs (single nucleotide polymorphisms) found in this region in AA women were also detected in an independent European American population of 1,195 cases and 1,164 controls. Findings from our study provide an example of how modifiable and non-modifiable factors may interact to influence fibroid risk and suggest a biological role for BMI in fibroid etiology.

The association between ultrasound-estimated visceral fat deposition and uterine fibroids: an observational study

Uterine fibroids are the most common neoplasm of the genital tract in reproductive women. Obesity holds a role as risk factor for uterine fibroids, through hormonal and inflammatory mechanisms. Visceral fat is a hormonally active tissue, so an increase in visceral fat may be considered as a risk factor, through the increased production of inflammatory mediators. The aim of the study was, therefore, to evaluate the association between the presence of uterine fibroids and fat tissue distribution, and to assess the efficacy of both anthropometric and instrumental indicators, in particular the sonographic measurement of preperitoneal fat thickness (PFT) and subcutaneous fat thickness (SFT). Study group consisted of childbearing-age women with at least one uterine fibroid with a diameter ≥10 mm (n = 71), all the childbearing-age women who access to the outpatient service of our institution in the same period, without evidence of uterine fibroids, constituted the control group (n = 145). A significantly difference in BMI (p = 0.0034), PFT (p < 0.0001), and SFT (p = 0.0003) emerged. At the multivariate analysis, only PFT showed an independent significant association with the presence of uterine fibroids (p < 0.0001). The ROC curve analysis identified a cut-off value of 6.7 mm of PFT as discriminator for the presence of uterine fibroids.

Influence of vitamin D and transforming growth factor β3 serum concentrations, obesity, and family history on the risk for uterine fibroids.

To evaluate the influence of 25-hydroxyvitamin D and transforming growth factor β3 (TGF-β3) serum concentrations, weight, and family history on the risk of developing uterine fibroids. Retrospective cohort study. University hospital. A total of 188 women, including patients admitted for uterine fibroid surgery (n = 105) as the study group and healthy women of similar age (n = 83) as controls. Medical history and completion of specially designed questionnaire, transvaginal or transabdominal genital ultrasound scan, blood sampling, and measurement of vitamin D and TGF-β3 serum concentrations. Evaluation of the impact of family history, vitamin D, and TGF-β3 serum concentrations on the risk of developing uterine fibroids. Mean 25-hydroxyvitamin D serum concentrations were 21.9 ± 8.9ng/mL and 26.7 ± 11.9ng/mL in patients with uterine fibroids and controls, respectively. The difference was statistically significant. The TGF-β3 serum concentrations in the fibroid-positive group ranged from 1.20 to 436.15 pg/mL (half the patients had concentrations >16.25 pg/mL). Concentrations in the control group ranged from 0.96 to 49.08 pg/mL (half the women had concentrations of >11.80 pg/mL). The differences were statistically significant. Higher body mass index (BMI) and positive family history were also found to be among the risk factors for uterine fibroids. Our study confirmed higher BMI, positive family history, and lower vitamin D and higher TGF-β3 serum concentrations as risk factors for uterine fibroids.

Induced and Spontaneous Abortion and Risk of Uterine Fibroids.

The relationship between abortion and uterine fibroids has received little attention. The aim of the present study was to explore the association between number of induced and spontaneous abortions and the risk of uterine fibroids in middle-aged and older Chinese women. A total of 14,595 retired female employees from the Dongfeng-Tongji cohort study were included in our analysis. Information on induced and spontaneous abortions was collected by trained interviewers through face-to-face interviews. Diagnosis of uterine fibroids was based on ultrasound or self-reported physician diagnosis of uterine fibroids. Logistic regression models were used to explore the associations between number of induced and spontaneous abortions and the risk of uterine fibroids. The prevalence of uterine fibroids was 15.1% among all participants. Higher number of induced abortions was associated with an increased risk of uterine fibroids (1 induced abortion: odds ratios [ORs] = 1.32, 95% confidence interval [CI] 1.18-1.48; 2 induced abortions: OR = 1.45, 95% CI 1.28-1.64; and ≥3 induced abortions: OR = 1.62, 95% CI 1.39-1.90). Compared with women without induced abortion, ORs for women with 1, 2, and ≥3 were 1.17 (95% CI 1.03-1.32), 1.21 (95% CI 1.06-1.39), and 1.36 (95% CI 1.15-1.61), respectively, after adjustment for potential confounders. No association was observed between the number of spontaneous abortions and the risk of uterine fibroids. The findings of this study showed that induced abortion may be an independent risk factor for uterine fibroids in middle-aged and older Chinese women.

Self-Reported Reproductive Tract Infections and Ultrasound Diagnosed Uterine Fibroids in African-American Women.

For decades, it has been hypothesized that reproductive tract infections (RTIs) are risk factors for uterine fibroids. However, only two recent studies have been conducted. We aimed to investigate the relationship between RTIs and fibroids in a large study using ultrasound screening for fibroids. We used cross-sectional enrollment data from African American women ages 23-34 years with no previous fibroid diagnosis. RTI history was measured by self-report and fibroid status by standardized ultrasound. Secondary fibroid outcomes were size, number, and total volume. Age- and multivariable-adjusted logistic regression were used to estimate odds ratios (ORs). In total, 1,656 women were included; 22% had fibroids. Bacterial vaginosis (BV) was associated with a 21% increased odds of fibroids [aOR 1.21, 95% confidence interval (CI) 0.93-1.58]. Chlamydia infection and pelvic inflammatory disease were associated with a 38% (aOR 0.62, 95% CI 0.40-0.97) and a 46% (aOR 0.54, 95% CI 0.25-1.17) reduced odds of having two or more fibroids, respectively. Those with a previous BV diagnosis had a 47% increased odds of having 2 or more fibroids (aOR 1.47, 95% CI 0.98-2.21) and a 41% increased odds of having a larger total fibroid volume (aOR 1.41, 95% CI 0.98-2.04). Our study was the first to explore the relationship between RTIs and fibroid size, number, and total volume. There appeared to be no strong associations between self-reported RTIs and fibroids. Studies using serology, a biochemical measure of past infection, are needed to better investigate associations between RTIs and fibroids.

Comparison of characteristics of fibroids in African American and white women undergoing premenopausal hysterectomy

To compare pathologic characteristics and epidemiologic risk factors for uterine fibroids in African American and white women undergoing hysterectomy. Cross-sectional analysis of women undergoing premenopausal hysterectomy. Two university-associated hospitals in North Carolina. African American (n = 225) and white women (n = 135) with fibroid diagnosis. None. Data were obtained from an in-person interview and abstracted from operative and pathologic reports. Analysis of variance and multiple linear regression models were used to identify characteristics associated with higher uterine weight, greater number of fibroids, and size of the largest fibroid. African American women had substantially more fibroids (9.9 vs. 4.5) with a concomitant higher mean uterine weight (477 vs. 267 g). Although African American women had a higher prevalence of established risk factors for fibroids, such as high body mass index (BMI) and hypertension, these factors were not associated with larger uteri or more numerous fibroids. In multiple linear regression models, the only factors statistically significantly associated with higher uterine weight, larger fibroids, and more numerous fibroids were race and nulligravidity. The presentation of fibroids as measured by uterine size or number of fibroids is more severe in African American women compared with white women. The differences in presentation cannot be explained by racial differences in the prevalence of known risk factors. Additional research is needed on environmental and genetic factors that may increase the risk for fibroids.

Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol- O-methyltransferase

To evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro. Laboratory study. University hospitals. Not applicable. Not applicable. HuLM cells were treated with 1,25-dihydroxyvitamin D3 (vitamin D), and cell proliferation was assayed by the methylthiazolyl tetrazolium technique. proliferating cell nuclear antigen (PCNA), BCL-2, BCL-w, cyclin-dependent kinase (CDK) 1, and catechol-O-methyltransferase (COMT) protein levels were analyzed by Western blotting. COMT mRNA and enzyme activity were assayed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and high-performance liquid chromatography analysis, respectively. The role of COMT was evaluated in stable HuLM cells by silencing COMT expression. Vitamin D inhibited the growth of HuLM cells by 47±0.03% at 1 μM and by 38±0.02% at 0.1 μM compared with control cells at 120 hours of treatment. Vitamin D inhibited extracellular signal-regulated kinase activation and down-regulated the expression of BCL-2, BCL-w, CDK1, and PCNA. Western blot, RT-PCR, and enzyme assay of COMT demonstrated inhibitory effects of vitamin D on COMT expression and enzyme activity. Silencing endogenous COMT expression abolished vitamin D-mediated inhibition of HuLM cell proliferation. Vitamin D inhibits growth of HuLM cells through the down-regulation of PCNA, CDK1, and BCL-2 and suppresses COMT expression and activity in HuLM cells. Thus, hypovitaminosis D appears to be a risk factor for uterine fibroids.

An endocrine-disrupting chemical, fenvalerate, induces cell cycle progression and collagen type I expression in human uterine leiomyoma and myometrial cells

Fenvalerate (Fen), widely used for its high insecticidal potency and low mammalian toxicity, is classified as an endocrine-disrupting chemical. Recently, Fen has received great attention for its adverse effects on human reproductive health. In this study, we found that Fen (10 μM) had a stimulatory effect on the growth of both cell lines at 24 h compared with controls by MTS ( p < 0.01) and BrdU ( p < 0.01) assays in hormonally responsive uterine leiomyoma (UtLM) cells and normal uterine smooth muscle cells (UtSMC). Flow cytometry results showed that Fen enhanced the escape of cells from the G 0–G 1 checkpoint and promoted progression of both cell types into the S phase. An Annexin V assay showed that Fen had an anti-apoptotic effect on both cell types. By Real-time PCR, we found that collagen I mRNA expression increased ( p < 0.05) in Fen-treated cells compared to controls, although it was greater in UtLM tumor cells. Accordingly, Fen increased ( p < 0.05) collagen I protein levels in both cell lysate and supernatant when compared to controls. To further test the mechanism of Fen's effects, transactivation and competitive binding assays were done. The results showed Fen did not significantly stimulate luciferase activity at concentrations of 0.1 μM, 1.0 μM or 10.0 μM in either of the cell types. Competitive binding assays revealed that the affinity of Fen binding to estrogen receptors (ERs) was non-detectable compared to E 2. Our data show that Fen can stimulate the growth of both UtLM cells and UtSMC, which involves a combination of enhanced cell cycle progression and inhibition of apoptosis. Also this compound can increase collagen I expression, at both mRNA and protein levels. Interestingly, the ER is less likely involved in either the hyperplasia or extracellular matrix (ECM) overproduction induced by Fen. Our results indicate that Fen exposure could be considered a novel risk factor for uterine fibroids through molecular mechanisms that do not directly involve the ERs.